2OL2

High Resolution Structure of Native PCI in Space Group P21

2OL2 の概要

• エントリーDOI: 10.2210/pdb2ol2/pdb
• 関連するPDBエントリー: 1LQ8 2HI9
• 分子名称: Plasma serine protease inhibitor, GLYCEROL (3 entities in total)
• 機能のキーワード: serpin, hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P05154
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89151.45

構造登録者

Li, W.,Huntington, J.A. (登録日: 2007-01-18, 公開日: 2007-03-13, 最終更新日: 2023-08-30)

主引用文献

Li, W.,Adams, T.E.,Kjellberg, M.,Stenflo, J.,Huntington, J.A.
Structure of native protein C inhibitor provides insight into its multiple functions.
J.Biol.Chem., 282:13759-13768, 2007

PubMed Abstract: Protein C inhibitor (PCI) is a multifunctional serpin with wide ranging protease inhibitory functions, unique cofactor binding activities, and potential non-inhibitory functions akin to the hormone-transporting serpins. To gain insight into the molecular mechanisms utilized by PCI we developed a robust expression system in Escherichia coli and solved the crystal structure of PCI in its native state. The five monomers obtained from our two crystal forms provide an NMR-like ensemble revealing regions of inherent flexibility. The reactive center loop (RCL) of PCI is long and highly flexible with no evidence of hinge region incorporation into beta-sheet A, as seen for other heparin-binding serpins. We adapted an extrinsic fluorescence method for determining dissociation constants for heparin and find that the N-terminal tail of PCI and residues adjacent to helix H are not involved in heparin binding. The minimal heparin length capable of tight binding to PCI was determined to be chains of eight monosaccharide units. A large hydrophobic pocket occupied by hydrophobic crystal contacts was found in an analogous position to the hormone-binding site in thyroxine-binding globulin. In conclusion, the data presented here provide important insights into the mechanisms by which PCI exercises its multiple inhibitory and non-inhibitory functions.

PubMed: 17337440
DOI: 10.1074/jbc.M701074200

実験手法

X-RAY DIFFRACTION (2 Å)